From 1dc373b9d0951a3df4411d651a0ce023aa17994f Mon Sep 17 00:00:00 2001
From: flannick <flannick@348d0f76-0448-11de-a6fe-93d51630548a>
Date: Tue, 10 Aug 2010 19:36:34 +0000
Subject: [PATCH] Initial implementation of evaluator to compute popgen theta
 statistics

git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@4004 348d0f76-0448-11de-a6fe-93d51630548a
---
 .../varianteval/ThetaVariantEvaluator.java    | 136 ++++++++++++++++++
 1 file changed, 136 insertions(+)
 create mode 100644 java/src/org/broadinstitute/sting/gatk/walkers/varianteval/ThetaVariantEvaluator.java

diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/varianteval/ThetaVariantEvaluator.java b/java/src/org/broadinstitute/sting/gatk/walkers/varianteval/ThetaVariantEvaluator.java
new file mode 100644
index 000000000..4ce203de9
--- /dev/null
+++ b/java/src/org/broadinstitute/sting/gatk/walkers/varianteval/ThetaVariantEvaluator.java
@@ -0,0 +1,136 @@
+package org.broadinstitute.sting.gatk.walkers.varianteval;
+
+import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker;
+import org.broadinstitute.sting.gatk.contexts.AlignmentContext;
+import org.broadinstitute.sting.gatk.contexts.ReferenceContext;
+import org.broad.tribble.util.variantcontext.VariantContext;
+import org.broad.tribble.util.variantcontext.Genotype;
+import org.broad.tribble.util.variantcontext.Allele;
+import org.broadinstitute.sting.playground.utils.report.tags.Analysis;
+import org.broadinstitute.sting.playground.utils.report.tags.DataPoint;
+import java.util.concurrent.ConcurrentMap;
+import java.util.concurrent.ConcurrentHashMap;
+
+@Analysis(name = "Theta Variant Evaluator", description = "Computes different estimates of theta based on variant sites and genotypes")
+public class ThetaVariantEvaluator extends VariantEvaluator {
+
+    @DataPoint(name = "avg_heterozygosity", description = "Average heterozygosity at variant sites; note that missing genotypes are ignored when computing this value")
+    double avgHet = 0.0;
+    @DataPoint(name = "avg_pairwise_diffs", description = "Average pairwise differences at aligned sequences; averaged over both number of sequeneces and number of variant sites; note that missing genotypes are ignored when computing this value")
+    double avgAvgDiffs = 0.0;
+    @DataPoint(name = "sum_heterozygosity", description = "Sum of heterozygosity over all variant sites; divide this by total target to get estimate of per base theta")
+    double totalHet = 0.0;
+    @DataPoint(name = "sum_pairwise_diffs", description = "Sum of pairwise diffs over all variant sites; divide this by total target to get estimate of per base theta")
+    double totalAvgDiffs = 0.0;
+    @DataPoint(name = "theta_region_num_sites", description = "Theta for entire region estimated based on number of segregating sites; divide ths by total target to get estimate of per base theta")
+    double thetaRegionNumSites = 0.0;
+
+		//helper variables
+		double numSites = 0;
+
+    public ThetaVariantEvaluator(VariantEvalWalker parent) {
+        super(parent);
+    }
+
+    public boolean enabled() {
+        return true;
+    }
+
+    public String getName() {
+        return "theta";
+    }
+
+    public int getComparisonOrder() {
+        return 1;
+    }
+
+    public String update1(VariantContext vc, RefMetaDataTracker tracker, ReferenceContext ref, AlignmentContext context) {
+
+				if (vc == null || !vc.isSNP() || !vc.hasGenotypes()) {
+						return null; //no interesting sites
+				}
+
+				if (vc.hasGenotypes()) {
+
+						//this maps allele to a count
+						ConcurrentMap<String, Integer> alleleCounts = new ConcurrentHashMap<String, Integer>();
+
+						int numHetsHere = 0;
+						float numGenosHere = 0; 
+						int numIndsHere = 0;
+
+						for (Genotype genotype : vc.getGenotypes().values()) {
+								numIndsHere++;
+								if (!genotype.isNoCall()) {
+										//increment stats for heterozygosity
+										if (genotype.isHet()) {
+												numHetsHere++;
+										}
+
+										numGenosHere++;
+										//increment stats for pairwise mismatches
+
+										for (Allele allele : genotype.getAlleles()) {
+												if (allele.isNonNull() && allele.isCalled()) { 
+														String alleleString = allele.toString();
+														alleleCounts.putIfAbsent(alleleString, 0);
+														alleleCounts.put(alleleString, alleleCounts.get(alleleString) + 1);
+												}
+										}
+								}
+						}
+						if (numGenosHere > 0) { 
+								//only if have one called genotype at least
+								this.numSites++;
+
+								this.totalHet += numHetsHere / numGenosHere;
+
+								//compute based on num sites
+								float harmonicFactor = 0;
+								for (int i = 1; i <= numIndsHere; i++) { 
+										harmonicFactor += 1.0 / i;
+								}
+								this.thetaRegionNumSites += 1.0 / harmonicFactor;
+
+								//now compute pairwise mismatches
+								float numPairwise = 0;
+								float numDiffs = 0;
+								for (String allele1 : alleleCounts.keySet()) {
+										int allele1Count = alleleCounts.get(allele1);
+
+										for (String allele2 : alleleCounts.keySet()) {
+												if (allele1.compareTo(allele2) < 0) {
+														continue;
+												}
+												if (allele1 .compareTo(allele2) == 0) {
+														numPairwise += allele1Count * (allele1Count - 1) * .5;
+
+												}
+												else {
+														int allele2Count = alleleCounts.get(allele2);
+														numPairwise += allele1Count * allele2Count;
+														numDiffs += allele1Count * allele2Count;
+												}
+										}
+								}
+
+								if (numPairwise > 0) {
+										this.totalAvgDiffs += numDiffs / numPairwise;
+								}
+						}
+				}
+
+        return null;
+    }
+
+    @Override
+    public void finalizeEvaluation() {
+
+				if (this.numSites > 0) { 
+
+						this.avgHet = this.totalHet / this.numSites;
+						this.avgAvgDiffs = this.totalAvgDiffs / this.numSites;
+						
+				}
+    }
+}
\ No newline at end of file